Obrezanova O.,Biologics |
Arnell A.,Biologics |
De La Cuesta R.G.,Biologics |
De La Cuesta R.G.,F-star Biotechnology Limited |
And 4 more authors.
mAbs | Year: 2015
Aggregation is a common problem affecting biopharmaceutical development that can have a significant effect on the quality of the product, as well as the safety to patients, particularly because of the increased risk of immune reactions. Here, we describe a new high-throughput screening algorithm developed to classify antibody molecules based on their propensity to aggregate. The tool, constructed and validated on experimental aggregation data for over 500 antibodies, is able to discern molecules with a high aggregation propensity as defined by experimental criteria relevant to bioprocessing and manufacturing of these molecules. Furthermore, we show how this tool can be combined with other computational approaches during early drug development to select molecules with reduced risk of aggregation and optimal developability properties. © Olga Obrezanova, Andreas Arnell, Ramón Gómez de la Cuesta, Maud E Berthelot, Thomas RA Gallagher, Jesús Zurdo, and Yvette Stallwood.
Ren X.,Eli Lilly and Company |
Guo Q.,Eli Lilly and Company |
Malabunga M.,Eli Lilly and Company |
Guernah I.,Eli Lilly and Company |
And 7 more authors.
DMM Disease Models and Mechanisms | Year: 2016
Activating mutations in fibroblast growth factor receptor 3 (FGFR3) have been identified in multiple types of human cancer and in congenital birth defects. In human lung cancer, fibroblast growth factor 9 (FGF9), a high-affinity ligand for FGFR3, is overexpressed in 10% of primary resected non-small cell lung cancer (NSCLC) specimens. Furthermore, in a mouse model where FGF9 can be induced in lung epithelial cells, epithelial proliferation and ensuing tumorigenesis is dependent on FGFR3. To develop new customized therapies for cancers that are dependent on FGFR3 activation, we have used this mouse model to evaluate a human monoclonal antibody (D11) with specificity for the extracellular ligand-binding domain of FGFR3, that recognizes both human and mouse forms of the receptor. Here, we show that D11 effectively inhibits signaling through FGFR3 in vitro, inhibits the growth of FGFR3-dependent FGF9-induced lung adenocarcinoma in mice, and reduces tumorassociated morbidity. Given the potency of FGF9 in this mouse model and the absolute requirement for signaling through FGFR3, this study validates the D11 antibody as a potentially useful and effective reagent for treating human cancers or other pathologies that are dependent on activation of FGFR3. © 2016. Published by The Company of Biologists Ltd.
Hasenhindl C.,University of Natural Resources and Life Sciences, Vienna |
Traxlmayr M.W.,University of Natural Resources and Life Sciences, Vienna |
Wozniak-Knopp G.,University of Natural Resources and Life Sciences, Vienna |
Jones P.C.,F-star Biotechnology Limited |
And 3 more authors.
Protein Engineering, Design and Selection | Year: 2013
Antigen-binding Fc fragments (Fcab) are generated by engineering the C-terminal loop regions in the CH3 domain of human immunoglobulin G class 1-crystallizable fragment (IgG1-Fc). For an optimum library design with high percentage of well-folded clones for efficient binder selection, information about the correlation between primary structure and stability is needed. Here, we present a rapid method that allows determination of the overall stability of whole libraries of IgG1-Fc on the surface of yeast by flow cytometry. Libraries of IgG1-Fc mutants with distinct regions in AB-, CD- and EF-loops of the CH3 domains randomized or carrying therein insertions of five additional residues were constructed, incubated at increasing temperatures and probed for residual binding of generic Fc ligands. Calculated temperatures of half-maximal irreversible denaturation of the libraries gave a clear hierarchy of tolerance to randomization of distinct loop positions. Experimental data were evaluated by a computational approach and are discussed with respect to the structure of IgG1-Fc and variation in sequence and length of these loops in homologous Fc proteins. Generally, the described method allows for quick assessment of the effects of randomization of distinct regions on the foldability and stability of a yeast-displayed protein library. © The Author 2013. Published by Oxford University Press. All rights reserved.
News Article | October 23, 2013
CAMBRIDGE, England--(BUSINESS WIRE)--F-star, an oncology-focused biopharmaceutical company, today announced the formation of F-star Alpha Ltd., an independent company which has been granted exclusive licences to a range of oncology assets from F-star Biotechnology Ltd. Under the terms of the licence agreement, F-star Alpha receives an exclusive licence to FS102, an Fcab™ antibody fragment, which eliminates HER2-positive cancer cells through a novel apoptotic mechanism of action. Furthermore, a genetic predictive biomarker has been identified, which allows selection of patients likely to respond to therapy. FS102 is now progressing to clinical testing in breast, gastric and colorectal cancer. In addition, F-star Alpha receives a licence for the generation of Fcabs or bispecific antibodies (mAb2™) against up to 22 other oncology and immuno-oncology targets. In return, F-star will receive a combination of milestone payments and tiered royalties. F-star Alpha is funded through a Series A investment of €9.4m from Atlas Venture, Aescap Venture, TVM Capital, SR One, MP Healthcare Venture Management, and MS Ventures. This investment enables the company to carry out IND-enabling studies with FS102. In addition the investment will fund the discovery of novel immuno-oncology therapies aimed at activating the patient’s immune system against cancer. “We are very pleased to announce the creation and funding of F-star Alpha, the first asset-centric vehicle, which exclusively comprises key assets of the F-star family”, said John Haurum, CEO of F-star. “The F-star technology platform has fully matured and enables the development of a large number of novel therapeutic products for the benefit of patients. This new company structure will accelerate the development of an exciting pipeline of cancer therapeutics, while creating greater commercial and financial flexibility for F-star, the investors, and future partners”. F-star is a biopharmaceutical company dedicated to developing novel bispecific antibody products that provide a significant improvement over the current standard of care. Given its strong patent position, it is the only biopharmaceutical company with the ability to create and develop Fcab™ antibody fragments, and bispecific antibodies, by modifying the constant region of an antibody. In particular, F-star’s Modular Antibody Technology™ enables rapid discovery and development of bispecific antibodies by introducing additional binding sites to the constant region of an antibody and offers unprecedented ease in the development and manufacturing of bispecific monoclonal antibodies. Using the Modular Antibody Technology™, F-star generates bispecific antibodies (mAb2™) that possess the favourable characteristics of traditional monoclonal antibodies, without the production challenges often associated with other antibody formats. F-star is now applying its proprietary technology to the development of a pipeline of product candidates. Since its founding in 2006 the company has secured funding and support from leading VC investors: Aescap Venture, Atlas Venture, Novo Ventures and TVM Capital; as well as from renowned strategic corporate investors: Merck Serono Ventures, MP Healthcare Venture Management and SR One. The company has major alliances with Boehringer Ingelheim and Merck Serono, each covering multiple targets. In 2011, F-star was selected by the industry newsletter FierceBiotech as one of the Fierce 15 winners, designating it as one of the most promising private biotechnology companies in the industry. F-star currently employs over 30 people at its research site in Cambridge, UK. FS102 is an Fcab which eliminates HER2-positive cancer cells through a novel mechanism of action in a defined patient population. FS102, works differently than current HER2-targeted therapies, and has potential to overcome resistance to these drugs. It binds to a discrete site on the HER2 molecule and induces HER2-positive tumour cells to undergo programmed cell death. In preclinical studies, FS102 shows remarkable efficacy at fighting HER2-positive cancer cells, including the complete elimination of tumours. F-star has also identified a well-defined biomarker, which would allow selection of patients that are likely to respond to therapy. FS102 is advancing toward clinical testing in breast, gastric, and colorectal cancer. Full preclinical data on FS102 is being presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, 21st October 2013.
News Article | April 20, 2015
F-star, the Cambridge UK oncology-focused biopharma company, has launched an independent spin-out business – F-star Beta – which has been granted exclusive licences to a range of oncology assets. F-star Beta is the second asset-centric vehicle created by the Babraham-based medical technology innovator. Under the terms of the licence agreement F-star Beta receives an exclusive licence for the generation of Fcab™ and bispecific antibodies (mAb2™) against certain oncology and immuno-oncology targets. In return, F-star will receive a combination of milestone payments and tiered royalties. John Haurum, CEO of F-star, said: “F-star created an asset-centric vehicle structure in October 2013 to accelerate the development of a pipeline of proprietary cancer therapeutics, while enabling greater commercial and financial flexibility for the company and future partners. “We are extremely pleased with the speed and productivity of our proprietary Modular Antibody Technology™ platform. The efficiency of our R & D engine facilitates the development of a large number of novel therapeutic products, well beyond what a single company can develop. “F-star Beta, as well as future asset-centric vehicles, is being established to create a flexible corporate structure to further enhance the opportunity to attract leading biopharmaceutical companies. “This approach was recently successful with our lead programme FS102 and the related agreement with Bristol-Myers Squibb to obtain an option to acquire our first asset-centric vehicle, F-star Alpha Ltd.”